Diacyl isothiocarbamide ether and method of producing same



Patented Apr. 24, 1928. i

UNITED STATES PATENT OFFICE.

HERBERT SCHOTTE, OF BERLIN-WILMERSDORF, GERMANY, ASSIGNOB TO THE FIRM CHEMISCHE IABRIK AUF .ACTIEN (VORM. E. SCEERING), OF BERLIN, GERMANY.

DIACYL ISOTHIOCABBAMIDE ETHER AND METI-IOD OF PRODUCING SAME.

Ho Drawing. Application filed July 12, 1928, Serial No. 122,043, and in Germany July 18', 1925.

My invention refers to new chemical con1- pounds being derivatives of thiocarbamide, and its particular object is the production of diacyl isothiocarbamide-S-alkyl ethers,

5 which hitherto had not been produced, and which are designed .to form intermediate products for 'usein the production of pharmaceutical and other preparations.

The investigations of 'Bernthsen and Klinger (Berichte d. deutsch. chem. Ges. 11/1878/493) as well as Claus (Berichte d. deutsch. chem. Ges. "8/1875/41) have shown the free alkyl ethers of isothiocarbamide to be very readily decomposable compounds.

15 While it is possible to obtain a solution of the free carbamide derivative, it has never been isolated in pure condition. In consequence thereof it had to be expected that the acylization of the carbamide derivative in a caustic alkaline medium would be difficult. Contrary to the results obtained by Wheeler and Johnson (J ourn. americ. chem. Soc. 29, 47 9, 1902) and Wheeler and Merriam (Journ. americ. chem. 'Soc. 23, 293, 1901) ,who in opf crating 1n the manner described only obtained monoacyl derivatives, I have succeeded in obtaining diacyl-S-alkyl isothiocarbamide by operating in accordance with Schotten-Baumann, however, the products obtained were soiled by acyl mcrcaptane and salts of thiocarbamide.

I have now ascertained that the acylization proceeds much easier and renders better yields, if acyl chloride is caused tosact on the solution of'a saltof a S-alkyl is0thiocar-- 5 bamide in a weak organic base, preferably in pyridine. For, in contradistinction to caustic alkali and to primary and secondary amines pyridin does not decompose the isothiocarbamide ethers and its acyl derivatives.

In practising my invention I prefer p'roceeding for instance as follows:

Ewample 1.

I N-CO- ClHl Example 2. 00

37 grams of S-ethyl isothiocarbamide are dissolved in about 200 grams of pyridine. To this solution is added a solutionof 80 grams of p-nitrobenzoyl chloride in ether and the mixture is .treatedfurther as/de- Eearmple 3. g If 37 grams of S-ethyl isothiocarbamide bromide are dissolved in ccms 'of pyoo can scribed! with reference to Example 1. The dinit-robenzoate of the S-ethyl isothiocarbamide is substantiall less readily soluble than the benzoate, an after bein purified by dissolving in alcohol melts under foaming at about 216 C. The reaction occurs according to the formula ridine under cooling-and 16 grams of acetyl chloride are added, there results the diacetate of S-ethyl.isothiocarbamide. 'The new compoiind forms an oilysubstance, disfidulty in water. and,'if'treated with primary .solving with diificulty in ether, more readior secondary amines, develops vmercaptane.

ly in alcohol and acetone, with great dif- The reaction occurs according to the formula Example 4. I chloro carbonate to form the dicarbethoxy 37 grams of S-ethyl isothiocarbamide bromide, on being dissolved in 100 ccms. of pyridine, will react with 45 grams of ethyl Example 5-.

22 grams of S-methyl-isothiocarbamide hydro iodide are dissolved in 80 ccms. of dry pyridine and grams of benzoyl chloride are slowly added under good cooling. Heating is preferably avoided in order to prevent derivative, which melts at about C. and

is soluble in ether only with great difliculty. The reaction occurs according to the formula v i i-000cm.

2 0.11m, H01 -oo-o can I and the crystals of 1,3-dibenzoyl -2-methyl thiocarbamide are freedv from the solutionby suction. They dissolve readily in acetone, ether and acetic ether, less readily in alcohol, are almost insoluble in' water, de-' i NH, n-co-omd-s-om mam-00.01 20am: s-om 20mm, 1101' H r --oo-o.H;

Example 6. heat. There is formed 1,3-diacetyl-1,2'-di 23 grams of S,N-dimethyl-isothiocarbamide hydro-iodide, on being dissolved in 100 methyl isothiocarbamide, an oily substance not fit for distillation, which is insoluble in water, but soluble in organic solvents. The

ccms. of pyridine, react with 16 grams of acetyl chloride under vlgorous generation of reactlon Occurs d g to the formula (I311: (I311: I rr-oo-om d-s-on; 2 cHvco-ol 2 cum: S0H| H '-co-oH| In place of pyridine also other weak organic bases such as dimethyl aniline or quinoline can be used. The analogous rethereof.

action will occur, if other salts of S-alkyl isothiocarbamide. are subjected to similar treatment.

Various changes may be made in the details of the operation and particularly in the proportions of t e ingredients present in the .solutions used Without departing from the invention or sacrificing the advantages I claim I 1. The method of producing diacyl isothiocarbamide-S-alkyl ethers bamide inpyridine.

comprising ing 37 grams of S-ethyl isothiocarbamide hydrobromide in 100 ccms. of dry pyridine and adding 56 parts of benzoyl chloride.

5. As a new product, the diacyl isothiocarbamide ethers having the formula x I l-00GB:

S-R1 I ICO-R2 wherein R, and R may be any univalent radicals either of the same or of a different kind, these ethers being neutral bodies dissolving only with diflibulty in water, being soluble in most organic solvents and colorless provided that no chromophoric groups are present in the molecule.-

7. As a new product, the diacetate of S- ethyl isothiocarbarnide, being an oily substance dissolving with difiiculty ,in ether, more readily in alcohol and acetone, with great difliculty in water and, if treated with primary or secondary amines, developing inercaptane.

8. As a new product, the diacyl isothiocarbainide ethers having the formula I! ILT-CO-B:

CSR1 IJI-CO-R: wherein R is any univalent radical and R any univalent aliphatic radicals, the products being colorless neutral bodies soluble in most organic solvents but dissolving in water only with difiiculty.

In testimony whereof I afiix my signature.

HERBERT SOHOTTE. 

